演題詳細

一般口演 / Oral Session

一般口演 25 (Oral Session 25) :CML:基礎 2

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日程
2013年10月11日(金)
時間
14:25 - 15:25
会場
第7会場 / Room No.7 (ロイトン札幌 2F リージェント)
座長・司会
中前 博久 (Hirohisa Nakamae):1
1:大阪市立大学大学院医学研究科 血液腫瘍制御学
 
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Dasatinib-induced LGL possibly correlates with TCRγ clonality and lower Treg ratio at diagnosis

演題番号 : OS-1-127

志村 勇司 (Yuji Shimura):1、堀池 重夫 (Shigeo Horiike):1、堤 康彦 (Yasuhiko Tsutsumi):2、初瀬 真弓 (Mayumi Hatsuse):3、岡野 晃 (Akira Okano):3、淵田 真一 (Shin-Ichi Fuchida):3、松本 洋典 (Yosuke Matsumoto):1、黒田 純也 (Junya Kuroda):1、高橋 良一 (Ryoichi Takahashi):4、志村 和穂 (Kazuho Shimura):5、兼子 裕人 (Hiroto Kaneko):2、西垣 光 (Hikari Nishigaki):6、魚嶋 伸彦 (Nobuhiko Uoshima):7、小林 裕 (Yutaka Kobayashi):8、島崎 千尋 (Chihiro Shimazaki):3、谷脇 雅史 (Masafumi Taniwaki):1

1:Dept. Hematology and Oncology, Kyoto Pref. Univ. of Medicine, Japan、2:Dept. Hematology, Japanese Red Cross Kyoto Daiichi Hospital, Japan、3:Dept. Hematology, Social Insurance Kyoto Hospital, Japan、4:Dept. Hematology, Omihachiman Community Medical Center, Shiga, Japan、5:Dept. Hematology, Aiseikai-Yamashina Hospital, Kyoto, Japan、6:Dept. Hematology, Fukuchiyama City Hospital, Japan、7:Dept. Hematology, Matsushita Memorial Hospital, Osaka, Japan、8:Dept. Hematology, Japanese Red Cross Kyoto Daiini Hospital, Japan

 

Introduction: Dasatinib, a 2nd-generation tyrosine kinase inhibitor (TKI), has specific effect of inducing large granular lymphocytes (LGL) in a part of patients. To investigate the clonality and clinical significance, we performed prospective and longitudinal analyses.
Methods: From Feb 2011 to Aug 2012, total of 20 patients with CML or Ph+ALL previously untreated or refractory/intolerant to first TKIs were enrolled in this study. TCRγ/δ clonality using PCR amplification according to BIOMED-2 standardization (Leukemia 2003) and phenotypical lymphocyte profiles were examined before and after TKIs induction.
Results: Seventeen (85%) had CML, and 16 patients were treated with dasatinib, the remaining 4 with nilotinib or imatinib. LGL lymphocytosis was observed in a half of dasatinib-treated cases, showing relation to increased attainment of CCyR within 6 months. NK cells were increased in 5, CTL in 1, and both type in 2 patients. In LGL+ group, TCRγ clones were frequently detected at diagnosis (6 of 8 cases) and persisted during therapy over 3 months, whereas only 3 of 12 showed clonal TCRγ which disappeared during disease course in LGL-group. TCRδ seemed to have no relationship with LGL expansion. Regulatory T cells (Treg, CD4+CD25+Foxp3+) ratio to helper T cells at diagnosis was lower in LGL+ than in LGL- group (median, 4.2% vs 6.6%), and the disparity was sustained through the therapeutic period.
Conclusion: TCRγ clonality at diagnosis and persistent identical clones was revealed in patients with LGL lymphocytosis, which may have relations to dasatinib effectiveness.

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